NMDA antagonists mimic the effects of clinically effective antidepressants in both preclinical tests predictive of antidepressant action and procedures designed to model aspects of depressive symptomatology. These findings led to experiments demonstrating that chronic administration of NMDA antagonists to rodents results in a downregulation of cortical β-adrenoceptors, a phenomenon also observed following chronic treatment with many antidepressants. These neurochemical and behavioral similarities between antidepressants and NMDA antagonists prompted us to examine the impact of chronic antidepressant treatment on NMDA receptors. Chronic (14 days) but not acute (1 day) administration of seventeen different antidepressants to mice produced adaptive changes in radioligand binding to NMDA receptors. Detailed studies with three antidepressants (imipramine, citalopram, and electroconvulsive shock) show that these changes develop slowly, persist for some time after cessation of treatment, and (for imipramine and citalopram) are dose dependent. Moreover, following chronic treatment with imipramine, these changes in radioligand binding to NMDA receptors appear restricted to the cerebral cortex. Based on the consistency of these effects across antidepressant treatments, we propose that adaptive changes in NMDA receptors may be the final common pathway for antidepressant action. The recent demonstration (Nowak et al., 1995) that radioligand binding to NMDA receptors is altered in frontal cortex of suicide victims (compared to age and post-mortem interval matched controls) is consistent with the hypothesis (Trullas and Skolnick, 1990) that this family of ligand gated ion channels is involved in the pathophysiology of depression.

From many points of view, zinc is one of the most important trace elements in biological systems. Many articles describe the well-known role of this metal in human physiology and pathophysiology, but in the related literature, there is a lack of current and reliable reviews of the role of zinc deficiency in many diseases. In this article, we describe the role of zinc deficiency in the oxidative stress control, immune response, proliferation, and pathogenesis and pathophysiology of selected diseases such as depression, cardiovascular diseases, diabetes mellitus, Alzheimer’s disease, and Wilson’s disease.